Methylation microarray-based detection of clinical copy-number aberrations in CLL benchmarked to standard FISH analysis.

Copy-number aberrations (CNAs) are assessed using FISH analysis in diagnostics of chronic lymphocytic leukemia (CLL), but CNAs can also be extrapolated from Illumina BeadChips developed for genome-wide methylation microarray screening. Increasing numbers of microarray data-sets are available from diagnostic samples, making it useful to assess the potential in CNA diagnostics. We benchmarked the limitations of CNA testing from two Illumina BeadChips (EPIC and 450k) and using two common packages for analysis (conumee and ChAMP) to FISH-based assessment of 11q, 13q, and 17p deletions in 202 CLL samples. Overall, the two packages predicted CNAs with similar accuracy regardless of the microarray type, but lower than FISH-based assessment. We showed that the bioinformatics analysis needs to be adjusted to the specific CNA, as no general settings were identified. Altogether, we were able to predict CNAs using methylation microarray data, however, with limited accuracy, making FISH-based assessment of deletions the superior diagnostic choice.

Adjuvant chemoradiation for high-grade cardiac leiomyosarcoma in a child: Case report and review of literature.

A 13-year-old healthy girl presented with dizziness and palpitations, found to have a left atrial mass. An 8-cm tumor was removed en bloc. Pathology confirmed grade 3 leiomyosarcoma with multifocal positive margins. She received adjuvant ifosfamide and doxorubicin, followed by concurrent proton radiotherapy and ifosfamide. Radiotherapy included 66 Gy (RBE) in 33 fractions to the operative bed. Prospectively graded toxicities included Grade 2 esophagitis and Grade 1 anorexia, dermatitis, and fatigue. She completed six cycles of ifosfamide. Two years post operation, she had no evidence of disease, intermittent palpitations with normal cardiac function, and no other cardiopulmonary or esophageal symptoms.

Quantifying in situ growth rate of a filamentous bacterial species in activated sludge using rRNA:rDNA ratio.

If the in situ growth rate of filamentous bacteria in activated sludge can be quantified, researchers can more accurately assess the effect of operating conditions on the growth of filaments and improve the mathematical modeling of filamentous bulking. We developed a method to quantify the in situ specific growth rate of Sphaerotilus natans (a model filament) in activated sludge using the species-specific 16S rRNA:rDNA ratio. Primers targeting the 16S rRNA of S. natans were designed, and real-time PCR and RT-PCR were used to quantify DNA and RNA levels of S. natans, respectively. A positive linear relationship was found between the rRNA:rDNA ratio (from 440 to 4500) and the specific growth rate of S. natans (from 0.036 to 0.172 h-1) using chemostat experiments. The in situ growth rates of S. natans in activated sludge samples from three water reclamation facilities were quantified, illustrating how the approach can be applied in a complex environment such as activated sludge.

Measures to reduce maintenance therapy with oral corticosteroid in adults with severe asthma.

BACKGROUND: Maintenance therapy with oral corticosteroid (OCS) is used, although not based on evidence, for patients with severe asthma, but OCS is associated with serious adverse effects; therefore, management strategies aimed at steroid sparing are important. OBJECTIVE: To provide an update on the evidence for OCS-sparing strategies in adults with severe asthma. METHODS: A systematic literature review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 21 studies (which comprised 3060 subjects) were included. Of the nonbiologic oral steroidsparing strategies (n = 5), the following lowered the OCS dose: Internet-based tapering strategy (44% reduction in OCS dose), inhaled corticosteroids (mometasone furoate [mean daily OCS dose reduction of 39% and 31% in patients treated with 800 mcg/day and 1600 mcg/day, respectively] and ciclesonide [OCS dose reduction of 47% and 63% in patients treated with 640 mcg/day and 1.280 mcg/day, respectively]), and methotrexate (OCS dose reduction of 55%). Of the biologic oral steroidtapering strategies (16 studies) the following agents lowered the OCS dose: cyclosporin A (62% reduction in OCS dose), masitinib (78% reduction in OCS dose), mepolizumab (50%83% reduction in OCS dose), and omalizumab (30%64% of enrolled patients achieved a reduction in OCS dose, and one study reported a dose reduction of 45%). CONCLUSIONS: In adults with severe asthma, several corticosteroid-sparing interventions were shown to be effective in reducing systemic steroid exposure, not least in studies of add-on biologic therapy. However, based on the available studies, ciclesonide, based on the low potential for systemic effect, especially seems to be a good candidate for reducing steroid exposure in these patients before possible initiation of biologic therapy.